Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited s...
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| Published in: | Clinical cancer research Vol. 27; no. 4; p. 1082 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
15.02.2021
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| ISSN: | 1557-3265, 1557-3265 |
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| Abstract | Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials.
Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC.
Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort.
Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis. |
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| AbstractList | Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials.PURPOSEMost patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials.Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC.EXPERIMENTAL DESIGNApplying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC.Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort.RESULTSPotentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort.Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.CONCLUSIONSCollectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis. Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials. Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC. Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort. Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis. |
| Author | Lee, Jaewon J Stephens, Bret M Bernard, Vincent Chang, Kyle Semaan, Alexander Weston, Brian R Huang, Jonathan Bhutani, Manoop S Maitra, Anirban Swartzlander, Daniel B Wong, Justin W Monberg, Maria E Scheet, Paul A Jakubek, Yasminka A Guerrero, Paola A |
| Author_xml | – sequence: 1 givenname: Alexander orcidid: 0000-0001-5424-3217 surname: Semaan fullname: Semaan, Alexander organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 2 givenname: Vincent orcidid: 0000-0003-1555-608X surname: Bernard fullname: Bernard, Vincent organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 3 givenname: Jaewon J orcidid: 0000-0002-5677-2398 surname: Lee fullname: Lee, Jaewon J organization: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 4 givenname: Justin W orcidid: 0000-0002-6803-1060 surname: Wong fullname: Wong, Justin W organization: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 5 givenname: Jonathan orcidid: 0000-0002-2867-3384 surname: Huang fullname: Huang, Jonathan organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 6 givenname: Daniel B surname: Swartzlander fullname: Swartzlander, Daniel B organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 7 givenname: Bret M surname: Stephens fullname: Stephens, Bret M organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 8 givenname: Maria E surname: Monberg fullname: Monberg, Maria E organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 9 givenname: Brian R orcidid: 0000-0002-9872-1687 surname: Weston fullname: Weston, Brian R organization: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 10 givenname: Manoop S orcidid: 0000-0002-1489-5947 surname: Bhutani fullname: Bhutani, Manoop S organization: Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 11 givenname: Kyle surname: Chang fullname: Chang, Kyle organization: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 12 givenname: Paul A surname: Scheet fullname: Scheet, Paul A organization: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 13 givenname: Anirban surname: Maitra fullname: Maitra, Anirban organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas – sequence: 14 givenname: Yasminka A orcidid: 0000-0003-1427-1015 surname: Jakubek fullname: Jakubek, Yasminka A email: paguerrero@mdanderson.org, yjakubek@mdanderson.org organization: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. paguerrero@mdanderson.org yjakubek@mdanderson.org – sequence: 15 givenname: Paola A surname: Guerrero fullname: Guerrero, Paola A email: paguerrero@mdanderson.org, yjakubek@mdanderson.org organization: Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, Texas |
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| Snippet | Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle... |
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| SubjectTerms | Aged Aged, 80 and over Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - mortality Carcinoma, Pancreatic Ductal - pathology Carcinoma, Pancreatic Ductal - therapy DNA Copy Number Variations DNA Mutational Analysis - methods Endoscopic Ultrasound-Guided Fine Needle Aspiration Feasibility Studies Female Genetic Heterogeneity Genomics Humans Male Middle Aged Mutation Pancreas - diagnostic imaging Pancreas - pathology Pancreatic Neoplasms - genetics Pancreatic Neoplasms - mortality Pancreatic Neoplasms - pathology Pancreatic Neoplasms - therapy Pilot Projects Prognosis Progression-Free Survival Whole Exome Sequencing |
| Title | Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples |
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